Enhancement of pradimicin production in Actinomadura hibisca P157-2 by metabolic engineering.

Abstract:

:Actinomadura hibisca P157-2 produces potent antifungal antibiotic pradimicins. To enhance pradimicin production, ACCase from Streptomyces coelicolor and two regulatory genes metK1-sp and afsR-sp from Streptomyces peuticus were overexpressed into A. hibisca using an integration vector pSET152 under the control of the strong ermE* promoter. The constructed plasmids pACC152, pSAM152, pAFS152, pSA152 and pASA152 were transformed into A. hibisca by the conjugal method. The recombinant strains A. hibisca ACC, A. hibisca SAM, A. hibisca AFS, A. hibisca SA and A. hibisca ASA produced greater amounts of pradimicin than the parental strain with an increment of 3-fold, 2.1-fold, 2.8-fold, 3.4-fold, and 4.5-fold respectively. To increase the acetyl-coA pool, the strains were fed methyl oleate and acetate as carbon sources. The production was increased in wild-type A. hibisca, A. hibisca ACC and A. hibisca ASA by 2.2-fold, 4.12-fold and 5.98-fold respectively, with oleate and by 1.12-fold, 3.8-fold and 5.38-fold respectively with acetate. The strain A. hibisca ASA remained the best strain for the production of pradimicin. The higher transcriptional levels of structural genes in the strains harboring metK1-sp and afsR-sp compared to the wild-type strain were consistent with the enhanced production.

journal_name

Microbiol Res

journal_title

Microbiological research

authors

Paudel S,Lee HC,Kim BS,Sohng JK

doi

10.1016/j.micres.2011.02.007

subject

Has Abstract

pub_date

2011-12-20 00:00:00

pages

32-9

issue

1

eissn

0944-5013

issn

1618-0623

pii

S0944-5013(11)00021-8

journal_volume

167

pub_type

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